The efficacy of Beta-Alanine, a literature review - By Yours Truly

[LockItUp]

This is taken directly from another forum, Intensemuscle, and is also from my introduction thread I started in muscle central today. I figured, this section might be appropriate for those seeking some literature.

So, if anyone doesn't know, I am pursuing my PhD in Physiology (ex phys to be more precise). I do a ton of writing and researching/lab work for school, and a part of our school is to write literature reviews ALL THE FREAKING TIME.
For the laymen, a lit review is basically an overview of a topic put together from already established research studies. The following is my literature review on beta-alanine...something I find very interesting. AND, since I am not worrying about getting this published in anyway (could care less if I am credited for putting it together, as it's just a narrative review of previously obtained data), I figured I would share.

Now, this isn't the entire review, as I have edited a good bit out on the sections that deal with just what exactly beta alanine is, and just how it works (pathways, receptors, enzymes etc) because it's a VERY dry read. But what I am posting is gonna be interesting to many people here.

Without further Adieu, here is the slightly edited version. oh, and by the way My name is Marc Sestok.

UNIVERSITY OF PITTSBURGH

The efficacy of Beta Alanine as an Ergogenic aid in Exercise and Sport


Literature Review

Marc Sestok


December, 2011

ABSTRACT:
In this literature review, the overall effectiveness of the amino acid Beta Alanine as an ergogenic aid is discussed. The current knowledge and background information on the uses of beta alanine in exercise settings are presented in the following review. The physiologic response to the introduction of beta alanine into the human body and the potential benefits derived from such supplementation are also presented. It has been demonstrated that the primary use of beta alanine in sport performance settings is the ability of the amino acid to help buffer blood lactate. Following this information regarding the uses of beta alanine, reviews of past studies and outcomes presented by these studies are addressed. Lastly, a discussion on potential future research questions is given by the reviewer.


 
The efficacy of Beta Alanine as an Ergogenic aid in Exercise and Sport

The sport supplement industry is a notoriously lucrative market, which generated over $22.5 billion in the year 2006 alone (Dobson & DaVanzo 2009). One of the most prominent sport supplements today, the amino acid beta-alanine has shown promise in becoming the next staple supplement in an athlete’s supplement arsenal to delay onset of fatigue. Beta-alanine’s prowess as an ergogenic aid arises from the effects on skeletal muscle’s acute physiologic response to exercise, most notably the generation of the dipeptide carnosine (beta-alanyl-L-histidine).

Carnosine consists of the amino acids beta-alanine and histidine. Found primarily in skeletal muscle and brain tissue, carnosine is formed by the bonding of beta-alanine and histidine through a reaction catalyzed by carnosine synthase, which is a naturally occurring reaction (Sale, C., Saunders, B., & Harris, R. 2010). The primary use of carnosine within skeletal muscle is as a pH buffer for lactic acid. This primary use was documented by Bate-Smith (1938) who showed carnosine to have side chain acid disassociation content of 6.83, indicating carnosine as a proper buffer for blood over the physiological pH range. Due to this buffering capacity, carnosine has relevance in sports performance in helping delay the onset of the lactate threshold due to increased blood acidity. However, direct carnosine supplementation is ineffective as a performance aid due rapid degradation upon oral ingestion via the hydrolyzing enzyme carnosinase (Hoffman et al, 2008). Therefore, increasing skeletal muscle carnosine must be completed through a different mechanism than direct supplementation of carnosine; beta-alanine supplementation is utilized to achieve an increase in intramuscular carnosine .

Even though the combination of beta-alanine and histidine is what comprises carnosine, supplementation of beta-alanine alone helps promote increased levels of carnosine in skeletal muscle. Since carnosine has a greater affinity for histidine and plasma levels of histidine are universally higher than that of beta-alanine, it is beta alanine that establishes itself as the rate-limiting substrate of carnosine synthesis ( Horinshi H, Grillo M, Margolis Fl. 1978, Ng , Marshall FD 1978). Hence, beta-alanine and not histidine is used in sports performance settings as an ergogenic aid.
As previously described, the formation of carnosine in muscle tissue causes a buffering effect. Once blood pH levels reach an acidic state, via lactic acid accumulation, the body will be unable to eliminate the accumulated lactic acid and muscular fatigue will occur during intense exercise.
Supplementation of beta-alanine has been shown to increase time to exhaustion, which allows an athlete to elicit greater training effects derived from the increased capacity for workload. The purpose of this literature review is to present the efficacy of beta-alanine as an ergogenic aid in performance training and sport.

Supplementation and Skeletal Muscle Carnosine Concentrations

There are numerous avenues that researchers have investigated regarding the use of beta alanine as an ergogenic aid. Questions of beta alanine accumulation in muscle tissue, side effects, dose dependant relationships, and overall muscle carnosine saturation have been examined through studies.

Because of rapid degradation upon oral ingestion, carnosine’s rate of resynthesis in skeletal muscle is limited to the plasma concentrations of its constituent amino acids. This resynthesis is further limited in that beta-alanine, found in low concentrations naturally in plasma, has a high affinity for carnosine synthase (Skaper SD, Das S, Marshall FD, 1978). As mentioned previously, this is to say that beta alanine is the rate limiting agent in carnosine’s production.

Harris et al (2006) were among the first researchers to study the effects of carnosine levels through supplementation of beta alanine. During the study, Harris et al found a dose dependent side effect of beta alanine. This side effect was termed “flushing” and manifested as short term mild paraesthesia of the skin. This flushing was described as “an unpleasant prickly sensation on the skin that lasted about sixty minutes post ingestion” by subjects (Harris et al p. 281, 2006). This was the first and only side effect of beta alanine supplementation found to date.

The Harris study also concluded information on the time to peak concentration of plasma beta alanine. The study showed that, regardless of dose, the time to peak concentration was between thirty to forty minutes with the half-life of beta alanine being at a mean of twenty five minutes (Harris et al, 2006). The Harris study also compared the effects of four weeks of beta alanine supplementation to the effects of four weeks direct carnosine supplementation. The study utilized a placebo group, a beta alanine group and a carnosine group. The results showed that all groups had increased plasma carnosine levels. However, it was the carnosine group that showed the highest increases in plasma carnosine (Harris et al, 2006). These findings were said to be controversial, due to the possibility of subject adherence to supplementation protocol being low. Further, it had been established that the direct supplementation of carnosine is a waste to do the rapid degradation of carnosine upon oral ingestion in humans. These findings therefore caused investigators to delve deeper into the physiology behind intra-muscular carnosine concentration and the controversy surrounding the Harris four week comparison protocol caused a subsequent investigation into the matter by Hill et al (2007).

During the Hill study, skeletal muscle carnosine levels were assessed over a ten week period in cyclists via muscle biopsy. After four weeks of supplementation, levels of muscle carnosine were shown to be elevated 60% in subjects and again were shown to raise another 20% after ten weeks (Hill et al, 2007). Hill also demonstrated that further increases in carnosine could be seen in lengthier administration of beta alanine. Due to this evidence of longer supplementation with beta alanine resulting in an increased concentration of carnosine, it can be said that the findings presented by Harris et al are void because four weeks of beta alanine supplementation is simply too brief of a period to see a threshold level of carnosine storage in muscle tissue (Hill et al, 2007).

The aforementioned studies showed that beta alanine is effective in raising plasma concentration of carnosine, but further research needed to be conducted to establish how long the effects of supplementation lasted in the body after cessation of use. Baguet et al (2009) were the first to study this measure. Baguet et al tested the effects of beta alanine supplementation in fifteen untrained subjects over a six week period. Concentrations of carnosine were assessed in all subjects via proton magnetic resonance spectroscopy (Baguet et al, 2009). The findings were that plasma carnosine levels dropped 2-4% on average per week with mean concentrations remaining significantly elevated after three weeks of stoppage of supplementation (Baguet et al, 2009). After statistical analysis, some subjects were deemed to be “high” responders or “low” responders to beta alanine administration. This indicates individual variability within consumers and as such calls for case by case dosing protocol of beta alanine to elicit ergogenic effects. (Baguet et al, 2009).

The ergogenic effects of beta alanine supplementation cannot be assessed solely by looking at the effects on carnosine concentrations by the use of beta alanine; direct effects on exercise performance must be reviewed.

Effects on Acute Exercise performance

The physiological effect of beta alanine on performance has been shown to come from a group of different mechanisms. One such mechanism demonstrated by Jordan et al (2010) is beta alanine’s ability to buffer blood lactate accumulation during exercise. This study looked at seventeen recreational active men in their mid to late twenties. The subjects participated in graded treadmill tests both before and after a twenty eight day supplementation period of six grams of beta alanine per day (Jordan et al, 2010). The results showed an increased performance due to the delaying of the onset of blood lactate accumulation in the subjects which were given beta alanine and not a placebo. In another study conducted by Zoeller R.F. , Stout J.R., O’Kroy J.A., Torok D.J., and Mielke M, (2007) similar findings were reported, although creatine monohydrate was used in conjunction with beta alanine during the study. The findings by Zoeller et all can still be said to apply solely to beta alanine supplementation’s effect on blood lactate responses and not due to creatine because of the lack of evidence of creatine’s use as a buffer and the overabundance of beta alanine as one.

Beta alanine’s effect on power output has also been studied. Suzuki Y., Ito O., Mukai N., Takahashi H., and Takamatsu K. (2002) conducted a study looking at the effects on power intra-muscular carnosine levels had on maximal cycling. The study found that there was a direct relationship between the amount of muscular carnosine and the power output during the last stretch of a thirty second maximal cycling test (Suzuki et al, 2002). From this, Suzuki et al concluded that high intensity exercise performance could be improved by increasing the concentrations of plasma carnosine. Hoffman et al further showed this relationship in a study looking at twenty six collegiate football players (2008). During a modified Wingate test for maximal aerobic power, a trend for lower fatigue was seen in players who were administered beta alanine as well as a report of less feelings of fatigue in these players after the conclusion of the test (Hoffman et al, 2008). Thienen et al (2009) have also observed that beta alanine supplementation can have a positive effect on sprint power. During the study, Thienen et al observed twenty one participants who engaged in a 110 minute endurance test that consisted of intermittent stages of high and lower power outputs. Subjects were tested multiple times over an 8 week span. After a supplementation period of beta alanine, subjects were shown to increase their peak, mean, and final power outputs 11.2%, 4.9%, and 10.9% respectively (Thienen et al, 2009).

Another acute effect of exercise that has been assessed with the supplementation of beta alanine has to do with hormonal response. A study looking at the effects of thirty days of beta alanine supplementation on resistance exercise performance was conducted by Hoffman et al (2008). Along with direct comparison of exercise performance in both a placebo and test group, this study looked at the serum concentrations of growth hormone, testosterone, and cortisol levels in subjects performing 70% of their one repetition maximums on the free barbell squat exercise over a period of four weeks. Serum hormone levels were assessed at baseline, fifteen minutes post-exercise, and thirty minutes post-exercise. The findings of the study showed a 22% increase in the number of repetitions performed from baseline to the end of the study in the test group versus the placebo group (Hoffman et al, 2008). Elevations in growth hormone levels were similar in both placebo and test groups, cortisol levels were elevated in both groups, and testosterone levels remained unchanged in both groups (Hoffman et al, 2008). These findings indicate that while beta alanine supplementation can significantly improve time to exhaustion in resistance training, there is no endocrine response through supplementation of beta alanine. This helps classify beta alanine as different from other ergogenic aids such as those that boost hormonal profiles, an example of which can be seen through administration of anabolic steroids.

Summary
Beta alanine is an amino acid which helps the body in production of the dipeptide carnosine which is found in skeletal muscle tissue. It has been consistently shown that concentration of intra-muscular carnosine is correlated to exercise performance. Carnosine plays a vital role in blood lactate buffering, which in turn helps delay the onset of fatigue during exercise. Beta alanine supplementation has been shown throughout numerous studies to illicit a positive effect in delaying lactic acid accumulation during exercise and to reduce levels of fatigue during high intensity exercise in general. These positive effects are shown to be the direct result of increased skeletal muscle carnosine levels via the introduction of beta alanine.
Discussion

Though it has been shown to reduce fatigue in exercise, there are still questions to be asked regarding whether or not the supplementation of beta alanine can be beneficial to all types of athletes equally. The studies mentioned above did make use of different demographics of athletes ranging from football players, to cyclists, to recreationally active subjects, but the studies all utilized similar testing methods and all focused on the effects of time to fatigue. Even though some of the aforementioned studies did look at power output, more tests need to be conducted in establishing the effects of repeated maximal muscular strength tests and the use of beta alanine. This can show whether or not a type II muscle fiber dominant athlete can benefit as much as a type I fiber dominant athlete. This discrepancy can be seen in the results of studies looking at cyclists as opposed to sprinters. Even though some headway has been made into this discussion of fiber dominance in the studies looked at in this review, a clear cut answer remains to be seen and much more study is needed.

Though touched on slightly in some of the studies reviewed, the subject of combining beta alanine and other already established ergogenic aids is an interesting one. Perhaps there are combinations of other amino acids that, when used with supplementation, can yield an even greater synergistic training effect than simply supplementing with beta-alanine alone. Creatine was mentioned in some of the studies reviewed, but perhaps other aids, such as Nitrous Oxide boosters that have been shown to increase blood flow, can be used to enhance the effect of beta alanine.

Overall, the efficacy of beta alanine as an ergogenic aid has been tested thoroughly and proven to be a supplement worthy of use in elite level athletes. The only questions the remained unanswered are those that ask what can be done to absolutely maximize the usefulness of beta alanine in performance settings.









References
Baguet A, Reyngoudt H, Pottier A, Everaert I, Callens S, Achten E, Derave W (2009) Carnosine loading and washout in human skeletal muscles. J Appl Physiol(106, Pp. 837–842)

Bate-Smith EC (1938). The buffering of muscle in rigour: protein, phosphate, and carnosine. J Physiol (92). Pp. 336-343.

Dobson DaVanzo & Associates, LLC, Joan E. DaVanzo, Ph.D., M.S.W., Steven Heath, M.P.A., Audrey El-Gamil, Allen Dobson, Ph.D. (2009) The Economic Contribution of the Dietary Supplement Industry - Analyses of the Economic Benefits to the U.S. Economy. Natural Products Foundation’s Dietary Supplement Information Bureau

Harris RC, Tallon MJ, Dunnett M, Boobis LH, Coakley J, Kim HJ, Fallowfield JL, Hill CA, Sale C, Wise JA (2006) The absorption of orally supplied b-alanine and its effect on muscle carnosine synthesis in human vastus lateralis. Amino Acids (30, Pp.279–289)

Hill CA, Harris RC, Kim HJ, Harris BD, Sale C, Boobis LH, Kim CK, Wise JA (2007) Influence of b-alanine supplementation on skeletal muscle carnosine concentrations and high intensity cycling capacity. Amino Acids(32, Pp. 225–233)

J. Hoffman, N. A. Ratamess, R. Ross, J. Kang, J. Magrelli,K. Neese, A. D. Faigenbaum, J. A. Wise (2008). β-Alanine and the Hormonal Response to Exercise. Int J Sports Med (29(12) pp. 952-958)
Horinshi H, Grillo M, Margolis Fl. (1978) Purification and characterization of carnosine synthetase from mouse olfactory bulbs. J Neurochem. (31,4. Pp. 909-919)

Jordan et al. (2007) Effect of beta-alanine supplementation on the onset of blood lactate accumulation (OBLA) during treadmill running: Pre/post 2 treatment experimental design. Journal of the International Society of Sports Nutrition (7 ,pp. 20)

Ng RH, Marshall FD (1978). Regional and subcellular distribution of homocarnosine-carnosine sythetase in the central nervous system of rats. J Neurochem. ( 30, 1. Pp. 187-190.)

Sale, C., Saunders, B., & Harris, R. (2010) Effect of beta-alanine supplementation on muscle carnosine concentrations and exercise performance. Amino Acids, 39,(2). pP. 321-333.
Skaper SD, Das S, Marshall FD (1973) Some properties of a homocarnosine-carnosine synthetase isolated from rat brain. J Neurochem 2, Pp. 1429–1445

Suzuki Y, Ito O, Mukai N, Takahashi H, Takamatsu K (2002) High levels of skeletal muscle carnosine contributes to the latter half of exercise performance during maximal cycle ergometer sprinting. Jpn J Physiol (52, pp. 199–205)

van Thienen R, van Proeyen K, vanden Eynde B, Puype J, Lefere T, Hespel P (2009) b-alanine improves sprint performance in endurance cycling. Med Sci Sports Exerc (41, Pp. 898–903)

Zoeller R.F. , Stout J.R., O’Kroy J.A.,Torok D.J., and Mielke M, (2007) Effects of 28 days of beta-alanine and creatine monohydrate supplementation on aerobic power, ventilatory and lactate thresholds, and time to exhaustion. Amino Acids (33, pp. 505–510)
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[GDavis]

This stuff in high doses gives awful "tingles"

[LockItUp]

Correct, it's mild paraestesia cause by the enzyme reacting in the pathway, ending with histamine, an inflammatory marker. It's most likely this mechanism that causes the feeling; little micro swelling happening intramuscularly at a rapid rate. Similar to why taking Niacin also causes flushing, as they both work on pathways dealing with histamines.

[LockItUp]

Hmmm...I guess this is too dry a read for some. Anyone reading this: It's not that long, and most applies directly to bodybuilding purposes...go ahead, learn something!

[juggernaut]

A product called All in 1 has this same compound in it for recovery, but can be used for pre-workout.

[LockItUp]

Yes, many products have this INGREDIENT in them for a reason .